Douglas Jennings, PharmD, FCCP, FAHA
Douglas Jennings, PharmD, FCCP, FAHA
Douglas Jennings, PharmD, FCCP, FAHA, FACC, currently practices as the clinical pharmacy manager in heart transplant and mechanical circulatory support at New York Presbyterian Columbia University Medical Center. He is a past chair of the American College of Clinical Pharmacy (ACCP) Cardiology PRN, and he is a fellow of ACCP, the American Heart Association, and the American College of Cardiology.

What's the Best P2Y12 Inhibitor for STEMI Patients Undergoing PCI?

MAY 31, 2016
For patients presenting with acute ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (pPCI) is the preferred treatment modality over fibrinolytic therapy at most US centers.
 
As pPCI usually involves deployment of intracoronary stents (most commonly drug-eluting stents [DES]), rapid and effective antiplatelet therapy is required to prevent recurrent MI and acute stent thrombosis.

Historically, the cornerstone regimen for pPCI patients with DES deployment has been dual antiplatelet therapy with aspirin and clopidogrel. Even when given at loading doses as high as 600 mg, however, clopidogrel has a highly variable response and may not adequately inhibit platelets in all patients.
 
Three newer antiplatelet agents have all been proven to be superior to clopidogrel in reducing ischemic adverse events in the setting of PCI: prasugrel, ticagrelor, and cangrelor. For STEMI patients in particular, subgroup analyses from pivotal trials with prasugrel and ticagrelor demonstrated improved outcomes over clopidogrel. Even the European Society of Cardiology’s 2012 STEMI guidelines recommend them as preferred agents. 
 
Unfortunately, no head-to-head comparator trials of those newer antiplatelet agents have ever been conducted.

Recently, a group of investigators set out to compare outcomes in STEMI patients undergoing pPCI who were treated with the various P2Y12 receptor inhibitors by conducting a network meta-analysis. This type of analysis compares multiple treatments using both direct comparisons of interventions within trials and indirect comparisons across trials based on a common comparator.
 
All randomized and nonrandomized clinical trials enrolling STEMI patients undergoing pPCI with administration of a periprocedural P2Y12 inhibitor were included, while trials that didn’t have stratification of outcomes available by type of P2Y12 inhibitor were excluded. A total of 73 full-text references were screened and 37 studies involving a total of 88,402 STEMI patients were included in the final review. 
 
Outcomes at 1 month (22 studies, n= 60,783) suggested that prasugrel was associated with lower rates of major adverse cardiac events than clopidogrel (at standard dosing, high dosing, and upstream use) and ticagrelor. The analysis also found that prasugrel had lower mortality and MI rates than clopidogrel and standard ticagrelor, lower stroke risk than standard clopidogrel and standard or upstream ticagrelor, and lower stent thrombosis than standard or upstream clopidogrel. 

At 1-year (10 studies, n= 40,333), prasugrel was associated with lower mortality and adverse cardiac events than other P2Y12 inhibitors. Adverse events were particularly lower with prasugrel in studies where patients received bivalirudin and DES, but not a glycoprotein IIb/IIIa inhibitor.
 
It’s also worth noting that although the patient numbers for cangrelor were small, both prasugrel and ticagrelor had trends for superiority over cangrelor with respect to in-hospital adverse cardiac outcomes. 
 
While the results of this analysis suggest that prasugrel is the preferred second antiplatelet agent for patients presenting with STEMI who undergo pPCI, I must caution that this type of analysis isn’t a substitute for a randomized, head-to-head clinical trial. These results are thought-provoking and certainly hypothesis-generating, but they don’t definitively establish the superiority of prasugrel over other P2Y12 inhibitors. 
 
On the contrary, prasugrel has several limitations that other P2Y12 inhibitors don’t. For instance, it’s contraindicated in patients with a history of stroke or transient ischemic attach (TIA), and it must be used with caution in patients older than 75 years or those with low body weight (<60 kg). Also, in clinical trials with clopidogrel, prasugrel significantly increased the risk of surgical bleeding, whereas ticagrelor didn’t. Finally, prasugrel can’t be given until the patient is in the cath lab and the coronary anatomy has been defined.
 
Until additional data are available, I’d advocate that either ticagrelor or prasugrel can be considered as a preferred antiplatelet agent in patients undergoing pPCI for STEMI. I think that the patient’s characteristics (eg, history of stroke) should dictate which agent is chosen, though cangrelor should be reserved for the few who are unable to take oral therapy. 
 
In any case, pharmacists can play a key role in assessing patients and assisting prescribers with selecting the best antiplatelet agent and dosing strategy in patients presenting with STEMI. 
 
Reference
Rafique AM, et al. Optimal P2Y12 inhibitor in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a network meta-analysis. JACC Cardiovasc Interv. 2016 May 23;9(10):1036-1046. doi: 10.1016/j.jcin.2016.02.013.


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